Tirzepatide
A once-weekly dual GIP/GLP-1 receptor agonist licensed for type 2 diabetes and obesity. Produces the largest mean weight loss of any approved agent to date, at the cost of a dose-limiting gastrointestinal side-effect profile.
01 Overview
Tirzepatide activates two incretin receptors rather than one, which appears to underlie its larger effect on weight and glycaemia than single-agonist GLP-1 drugs.
The headline weight-loss figures are trial-grade and robust; the practical story is tolerability and what happens to lean mass when weight comes off quickly.
02 Mechanism
A synthetic 39-amino-acid peptide that agonises both the GIP and GLP-1 receptors. The combined action slows gastric emptying, enhances glucose-dependent insulin secretion, and reduces appetite through central pathways.
03 Dosing
| Tier | Dose | Route | Notes |
|---|---|---|---|
| Starting | 2.5 mg/wk | SubQ | Four-week initiation dose; not intended to be therapeutic, it exists to build tolerance. |
| Maintenance | 5–10 mg/wk | SubQ | Titrated upward in 2.5 mg steps no more often than every 4 weeks. |
| Maximum | 15 mg/wk | SubQ | Highest licensed dose; largest effect and highest discontinuation rate. |
04 Effects
| Effect | Magnitude | Evidence | |
|---|---|---|---|
| Weight lossSURMOUNT-1: mean 20.9% at 15 mg — the largest for any approved agent | ~20% at 72 weeks | Clinical | |
| Glycaemic controlSuperior to semaglutide in head-to-head trial (SURPASS-2) | HbA1c −2.0 to −2.3% | Clinical | |
| Appetite reductionCentral mechanism; the proximate cause of the weight effect | Marked | Clinical | |
| Improved cardiovascular markersOutcome trial (SURPASS-CVOT) reported; hard-endpoint data still maturing | BP, lipids | Observational |
05 Side effects
| Effect | Severity | Frequency | Evidence | Countermeasures |
|---|---|---|---|---|
| Gastrointestinal effectsNausea, vomiting, diarrhoea and constipation — the dose-limiting effect and the main driver of discontinuation. | Moderate | Very common | Clinical | |
| Lean mass lossA substantial fraction of rapid weight loss is lean tissue, as with any large calorie deficit. | Moderate | Common | Clinical | |
| Gallbladder diseaseCholelithiasis and cholecystitis, associated with rapid weight loss generally rather than the drug specifically. | Moderate | Uncommon | Clinical | |
| PancreatitisA rare but serious class-associated signal for incretin drugs. | Severe | Rare | Observational |